茚达特罗上市剂量选择的论战：美国FDA定量药理学审评的故事

长效β2受体激动剂（LABA）一直存在安全性争议,此类药物上市的剂量选择至关重要,定量药理学方法成为关键评价工具。茚达特罗在上市审评过程中,美国食品药品管理局(FDA)与企业的定量药理学家们针对相同的试验数据,分别建模获得不同的上市剂量决策,相互反驳,在学术刊物上论战,甚至刊物也发表述评,显然FDA的模型更有说服力。本例堪称定量药理学在新药审评决策中的精彩案例,充分展示了定量药理学优势,即在缺少头对头研究时,整合多个试验数据,通过建模和模拟,确定了最终上市剂量。同时也展示了定量药理学特性,如多学科交叉、专业性极强、分析过程复杂、对经验的要求,可以大胆假设,但务必小心求证。     

新药研发中定量药理学研究的价值及其一般考虑

定量药理学是利用建模与模拟技术对药代动力学、药效动力学、机体功能、疾病进程和试验过程等信息进行模型化研究的一门科学。其在新药研发中的早期介入和全程参与能够形成模型引导的药物研发模式，以提高研发和科学审评效率，降低研发成本，缩短新药上市时间。本文根据国内外应用实践，阐述了定量药理学在新药研发中的价值、研究特点、应用条件及操作规范，以期作为国内定量药理学研究的专家共识，为定量药理学在我国新药研发中的应用提供参考。     

安全药理学研究的基本要求及其规范化

安全药理学是从药理学、生理学和毒理学发展而来的一门独立的综合性药理学学科。安全药理学研究之目的是识别、监控并确定非临床研究中出现潜在的不期望的药效活性。本文分析安全药理学的现状, 讨论实验设计的基本要求, 对中枢神经系统、心血管系统和呼吸系统实验设计的规范化提出了建议。     

遗传药理学的学科发展与未来

个体化用药疗效差异现象的发现促成了遗传药理学的诞生, 并使药学研究的学科范式发生了根本性的改变。而基因组学研究的学术背景,使遗传药理学的核心概念得到系统证实。基因芯片技术等新知识载体和新技术的发展将使个体化用药的理论成为现实。     

阿尔兹海默病的疾病进展模型与研究进展

阿尔兹海默病（AD）是一种病理机制暂不明确的神经退行性疾病,定量药理学中的疾病进展模型可以通过定量的方法充分描述AD患者疾病发展轨迹。通过模型中引入生物标志物信息,可有助于加深对AD病理机制的研究,辅助并优化临床试验的设计。现已有多种经验性或半机制的AD疾病进展模型报道。本文对此进行了综述,以期为阿尔兹海默病的临床研究和新药研发提供参考。     

对临床药理学一些基本问题研究的思考

临床药理学是研究药物与人体相互作用及其规律的一门学科。临床药理学基本原理在药物的临床研究与评价、药物不良反应监测等方面做了大量工作,取得了明显进展。然而,对临床药理学的共性、关键性和前沿性的基本问题研究更应给予高度关注,在进一步做好常规性临床药理学服务工作的同时,积极加强临床药理学学术问题的探索,为临床安全有效合理用药提供理论支撑。药物相互作用、多药耐药(MDR)、遗传药理学、药物基因组学、药动学/药效学(PK/PD)模型、性别药理学、基于药物作用于人体病理组织细胞的药效学和分子机制的研究等临床药理学的共性、关键性和前沿性问题已引起人们的重视。本文就临床药理学研究的一些基本问题的思考作一简述。     

FDA儿科临床药理学研究指导原则简介

儿科临床药理学是临床药理学的一个重要内容,是儿科临床安全有效用药的理论基础,急待加速发展。FDA于2014年12月发布了《儿科临床药理学研究指导原则草案》,详细描述了儿科临床药理学的研究内容和方法。本文介绍该指导原则的主要内容,期望对促进我国儿科临床药理学发展和加强注册药品相应内容的管理有益。     

基因治疗用腺相关病毒载体的剂量效应与剂量控制

人类基因治疗需要在靶细胞适时、适量、安全的产生具有疗效的药物,这些正好是定量药理学的研究范畴。重组腺相关病毒载体(rAAV)具有的各种特性以及近来在规模化制备方面取得的进展使其逐渐成为基因治疗的理想载体。超过60项以AAV为载体的基因治疗已经完成或正在展开。其中,rAAV载体的剂量与基因表达效率以及临床疗效之间的关系是研究者关注的焦点之一。多数研究认为,在一定的剂量范围内,基因表达水平具有剂量依赖性。然而, 基因表达水平同时还受病毒载体构型、组织趋向性、细胞靶向性、注射途径, 甚至患者的年龄、性别等条件影响 ,基因表达水平还可受到其他药物的调控。因此,基因治疗实验过程中应结合定量药理学深入展开,解决基因治疗中的定量与药效之间的关系。     

与Hillert教授有关的材料科学基础课程知识点及他与北京科技大学的科研交流

瑞典皇家工学院的M. Hillert教授是北京科技大学最早聘请的名誉教授之一,他的研究领域很宽,材料科学基础（简称材科基）课程的一些知识点与他有关,如扩散控制的新相长大速度公式、晶粒长大原理、调幅分解及计算相图等。早在1980年他就来北京科技大学讲学,基于其讲稿翻译的《合金扩散与热力学》一书对我国材料工作者及学生产生重要影响。他在热力学计算相图方面的原创工作对北京科技大学相关领域产生重要影响,在计算相图方面还亲自培养了北京科技大学青年教师。本文基于材料科学基础课程的学习及北京科技大学的国际交往方面分析讨论了Hillert教授的一些贡献,希望对课程建设、青年教师对相关领域的背景了解有所帮助。     

全身麻醉药物遗传药理学研究进展

全身麻醉是指由多种全身麻醉药物引起的一系列无意识、记忆缺失、痛觉缺失、运动不能等状态。随着遗传药理学及药物基因组学的发展,全身麻醉中各类药物与自身遗传因素的关系越来越受到关注。本文对全身麻醉中常用的镇痛药、镇静催眠药、肌松药及止吐药的遗传药理学研究进行综述,归纳近年来的研究进展。     

Computational Materials Science and Engineering Education: An Updated Survey of Trends and Needs

We present a summary of the state of computational materials science and engineering (CMSE) education based on a survey of materials science department chairs, faculty with computational interests, and employers of materials scientists and engineers. This survey is an update of one previously conducted in Thornton et al. (JOM 61:12–17, 2009). Three questionnaires were distributed among department chairs, faculty, and employers. The surveys asked to rate the importance of incorporating CMSE into the undergraduate curriculum, how it should be incorporated, the current offerings in CMSE, how those offerings have recently changed, what software tools are taught/used, and what opportunities exist in CMSE education, along with freeform questions regarding experience in teaching CMSE and impact of CMSE education. The survey results revealed an increased availability of CMSE courses in most of the materials departments surveyed, and strong support for including CMSE into the core curriculum. They also indicated that there is no clear preference as to whether such incorporation into the core curriculum should be through standalone courses or through modules in existing courses. The resources used in these courses, including online tools and software, are also summarized. The responses from the computational faculty point to a continued need for modules, including software tools and educational materials, that can be readily implemented by materials faculty regardless of their area of expertise.     

大学治理中教师与行政人员的关系: 基于社会资本的研究

教师与行政人员的关系是大学治理研究中的重要问题。教师和行政人员之间的职业文化差异成为他们在决策时追求共同利益的障碍。社会资本的引入提供了新的分析视角。参与网络、组织信任是大学治理中重要的社会资本。中国大学要加速教师参与决策的制度化，从而增加治理中的社会资本。     

1+X背景下模具专业职业教育教学创新团队建设

在1+X证书制度试点工作的背景下,针对当前模具专业建设中突出的问题,从人才培养方案制定、课程开发、信息化教学改革、产教融合、师资队伍建设、保障措施等方面提出可行的建设举措,推进团队建设有序发展,将模具教师团队打造为教师、教材、教法"三教"改革的主力,为区域经济发展、全面提高复合型技术技能人才培养质量提供支撑。     

1+X背景下模具专业职业教育教学创新团队建设

在1+X证书制度试点工作的背景下,针对当前模具专业建设中突出的问题,从人才培养方案制定、课程开发、信息化教学改革、产教融合、师资队伍建设、保障措施等方面提出可行的建设举措,推进团队建设有序发展,将模具教师团队打造为教师、教材、教法"三教"改革的主力,为区域经济发展、全面提高复合型技术技能人才培养质量提供支撑。     

Computational materials science and engineering education: A survey of trends and needs

Results from a recent reassessment of the state of computational materials science and engineering (CMSE) education are reported. Surveys were distributed to the chairs and heads of materials programs, faculty members engaged in computational research, and employers of materials scientists and engineers, mainly in the United States. The data was compiled to assess current course offerings related to CMSE, the general climate for introducing computational methods in MSE curricula, and the requirements from the employers’ viewpoint. Furthermore, the available educational resources and their utilization by the community are examined. The surveys show a general support for integrating computational content into MSE education. However, they also reflect remaining issues with implementation, as well as a gap between the tools being taught in courses and those that are used by employers. Overall, the results suggest the necessity for a comprehensively developed vision and plans to further the integration of computational methods into MSE curricula.     

Effective training data selection in tool condition monitoring system

When neural networks (NNs) are used to identify tool conditions, the richness and size of training data are crucial. The training data set not only has to cover a wide range of cutting conditions, but also to capture the characteristics of the tool wear process. This data set imposes significant computing burdens, results in a complex identification model, and hampers the feasible application of NNs. In this paper, a training data selection method is proposed, and a systematic procedure is provided to perform this data selection. With this method, the generalization error surface is divided into three regions, and proper sampling factors are chosen for each region to prune the data points from the original training set. The quality of the training set is estimated by performance evaluation through decision making. In this work, SVM is used in the decision making method, and the generalization error is used as the performance evaluation criterion. The tradeoff between the generalization performance and the size of the training set is key to this selection. Experimental results have demonstrated that this selection strategy provides an effective and efficient training set, and the developed model based on this set is fast and reliable for tool condition identification.     

IFHTSE Global 21: Heat treatment and surface engineering in the twenty-first century Part 8 – Training in heat treatment and surface engineering

Abstract

It is well known that metallurgists, materials scientists and engineers all have some training in heat treatment and surface engineering (thermal processing) as an intrinsic part of their courses, irrespective of the qualification to which the course leads. However, for those who are going to work in the thermal processing industry or have responsibility for that area of their business, it has to be acknowledged that the level of training is not in sufficient depth to allow them to conduct the business in the best possible manner. In other words, additional training is required. How employees were trained some years ago is compared with the training that is available today, and measures to ensure that sufficient appropriately trained people are available to the industry in the future are proposed. Although the main thrust of this paper will be applicable to all businesses carrying out thermal processing, it is very much based on the author's experience of working for Bodycote, a major thermal processing service provider, for the past 31 years. My many discussions in both Europe and the USA with both colleagues and educators have led me to believe that the UK experience is far from unique.     

“双轨合一”培养模式对血液内科专业型硕士研究生影响的分析

目的：探讨“双轨合一”新政策下,新的培养模式对血液内科专业学位型硕士研究生的影响。方法：回顾性分析2013年1月－2018年9月在我院血液内科学习的硕士研究生。按培养模式将研究生分为“双轨合一”培养及“非双轨合一”培养两组,比较两组学生的医德医风、血液专业基础理论、临床技能、科研能力及就业情况。结果：两组研究生在医德医风方面成绩差异无统计学意义（P>0.05）;而“双轨合一”培养组研究生的专业理论考核成绩、临床诊疗及技能考核成绩均高于“非双轨合一”培养组（P<0.05）。“双轨合一”培养组研究生以第一作者发表论文比例明显少于“非双轨合一”培养组（P<0.05）;而两组在II类以上期刊发表论文比例上差异无统计学意义（P>0.05）。结论：“双轨合一”培养模式能提高专业型研究生的临床思维能力以及专科技能水平,但由于科研培训时间明显减少,导致其科研能力有所下降,提示在“双轨合一”培养体制中应注重研究生科研能力的培养,为研究型医院培养优秀人才。     

模具工职业标准在高职教育中的应用研究简

在对美国模具工职业标准研究的基础上,结合国内模具工职业标准,根据高职教育的特点,研究了职业标准在专业培养方案、课程开发以及学生技术技能培养等3个方面上应用。